To examine whether a mixed lipid emulsion reduces the incidence of parenteral nutrition associated cholestasis (PNAC) in extremely low birth weight (ELBW, 1.5 mg/dL [25 µmol/L] at 2 consecutive measurements). The study was powered to detect a reduction of PNAC from 25% to 10%. Reasons for noneligibility of 274 infants screened were refusal to participate (n = 16), death (n = 10), withdrawal of treatment (n = 5), higher order multiples (n = 9), and parents not available for consent (n = 4). Intention to treat analysis was carried out in 223 infants (7 infants excluded after randomization). Parenteral nutrition associated cholestasis was 11 of 110 (10.1%) in the intervention and 18 of 113 (15.9%) in the control group (P = .20). Multivariable analyses showed no statistically significant difference in the intention to treat (aOR 0.428, 95% CI 0.155-1.187; P = .10) or per protocol population (aOR 0.457, 95% CI 0.155-1.347; P = .16). There was no statistically significant effect on any other neonatal morbidity. The incidence of parenteral nutrition associated cholestasis was not significantly reduced using a mixed lipid emulsion in ELBW infants. ClinicalTrials.govNCT01585935.

Background: Parenteral nutrition associated cholestasis (PNAC) is a frequently observed pathology in extremely low birth weight (ELBW) infants. Its pathogenesis is determined by the composition and duration of parenteral nutrition (PN) as well as the tolerance of enteral feeds (EF). “Aggressive” nutrition is increasingly used in ELBW infants to improve postnatal growth. Little is known about the effect of “aggressive” nutrition on the incidence of PNAC. We analyzed the influence of implementing an “aggressive” nutritional regimen on the incidence of PNAC and growth in a cohort of ELBW infants.Methods: ELBW infants were nourished using a “conservative” (2005–6;n= 77) or “aggressive” (2007–9;n= 85) nutritional regimen that differed in the composition of PN after birth as well as the composition and timing of advancement of EFs. We analyzed the incidence of PNAC (conjugated bilirubin > 1.5 mg/dl (25 µmol/l)) corrected for confounders of cholestasis (i.e., NEC and/or gastrointestinal surgery, sepsis, birth weight, Z-score of birth weight, time on PN and male sex), growth until discharge (as the most important secondary outcome) and neonatal morbidities.Results: The incidence of PNAC was significantly lower during the period of “aggressive” vs. “conservative “nutrition (27% vs. 46%,P< 0.05; adjusted OR 0.275 [0.116–0.651],P< 0.01). Body weight (+411g), head circumference (+1 cm) and length (+1 cm) at discharge were significantly higher. Extra-uterine growth failure (defined as a Z-score difference from birth to discharge lower than −1) was significantly reduced for body weight (85% vs. 35%), head circumference (77% vs. 45%) and length (85% vs. 65%) (P< 0.05). The body mass index (BMI) at discharge was significantly higher (11.1 vs. 12.4) using “aggressive” nutrition and growth became more proportionate with significantly less infants being discharged below the 10th BMI percentile (44% vs. 9%), while the percentage of infants discharged over the 90th BMI percentile (3% vs. 5%) did not significantly increase.Discussion: “Aggressive” nutrition of ELBW infants was associated with a significant decrease of PNAC and marked improvement of postnatal growth.

Introduction: The aims of the study were to describe the neurodevelopmental outcome of extremely low birth weight (ELBW) infants with parenteral nutrition-associated cholestasis (PNAC) and to assess whether PNAC is associated with adverse neurodevelopmental outcome. Methods: The study is a secondary analysis of controlled trial (June 2012–October 2017) on PNAC incidence in ELBW infants receiving two different parenteral lipid emulsions (mixed lipid emulsion containing fish oil vs. soybean oil-based). Neurodevelopmental follow-up at 12- and 24-month corrected age was compared in infants with and without PNAC. A machine learning-based regression analysis was used to assess whether PNAC was associated with adverse neurodevelopmental outcome. Results: For assessment of neurodevelopmental outcome (Bayley-III), 174 infants were available at 12-month (PNAC: n = 21; no PNAC: n = 153) and 164 infants at 24-month (PNAC: n = 20; no PNAC: n = 144) corrected age. The neurodevelopment of ELBW infants with PNAC was globally delayed, with significantly lower cognitive, language, and motor scores at both 12- and 24-month corrected age. Regression analyses revealed that PNAC was associated with an adverse motor outcome. Conclusion: ELBW infants with PNAC are at increased risk for adverse neurodevelopmental outcome.

Blood transfusions are required by the majority of extremely premature infants. Packed red blood cells (PRBCs) are usually applied via simple peripheral cannulas. In situations where no peripheral venous access is achievable, 27 Gauge (G) neonatal PICC lines – that are ideally exclusively dedicated to application of parenteral nutrition – may represent a useful alternative access for PRBC transfusions. However, transfusion via small scaled catheters may damage PRBCs and lead to hemolysis. We here evaluate whether transfusion of irradiated PRBCs via 27 G PICC lines leads to hemolysis in vitro. Experimental transfusions of gamma-irradiated PRBCs were performed at increasing velocities (2.5, 3.7, 5 ml/h; full force manual push approximating 30 ml/h) via 27 G PICC lines of 20 and 30 cm length. Parameters of hemolysis (lactate dehydrogenase, potassium and free hemoglobin) were measured from the supernatants of transfused PRBCs and the percentage of hemolysis was calculated. Potassium and lactate dehydrogenase after transfusion at increasing velocities did not differ significantly from negative controls. Free hemoglobin levels showed a small but significant increase at the slowest transfusion speed (2.5 ml/h) using the 30 cm 27 G PICC line, with a relative hemolysis of only 0.13%. A manual push (approximating 30 ml/h) showed no significant changes of parameters from baseline. We conclude that transfusion of gamma-irradiated PRBCs using a 27 G neonatal PICC line does not cause clinically relevant hemolysis in vitro. Clinical studies are needed to confirm the feasibility and safety of the approach in vivo. Extrem unreife Frühgeborene benötigen oft mehrfach Bluttransfusionen, die normalerweise über periphere Venenverweil­katheter verabreicht werden. Ist kein peripherer Zugang möglich, könnten für die parenterale Ernährung gedachte 27 Gauge (G) peripher inserierbare Katheter (PICC) auch für Transfusionen verwendet werden. Der sehr enge Querschnitt dieser Katheter könnte jedoch zu einer Beschädigung der transfundierten Erythrozyten und zu Hämolyse führen. Experimentelle Transfusionen von bestrahlten Erythrozytenkonzentraten über 27-GPICC-Katheter (20 und 30 cm Länge) wurden mit definierten Geschwindigkeiten (2,5, 3,7, 5 ml/h und manuelle Transfusion mit ungefähr 30 ml/h) durchgeführt. Die Hämolyseparameter (Laktat-Dehydrogenase, Kalium und freies Hämoglobin) wurden in den Überständen der Erythrozyten nach Transfusion gemessen und die relative Hämolyse berechnet. Die nach Transfusion gemessenen Kalium und LDH-Werte zeigten keinen Unterschied zu den Negativkontrollen. Nur nach Transfusion über den 30-cm-27-G-PICC-Katheter mit der langsamsten Geschwindigkeit (2,5 ml/h) kam es zu einem minimalem, aber signifikanten Anstieg des freien Hämoglobins, mit einer relativen Hämolyse von nur 0,13%. Nach manueller Transfusion (ungefähr 30 ml/h) fand sich kein Anstieg der Hämolyseparameter. 27-G-PICC-Katheter wurden für Transfusionen in vitro ohne Hinweis auf relevante Hämolyse verwendet. Eine Evaluation in der Klinik bezüglich der Machbarkeit und Sicherheit steht aus.